Fractionated Stereotactic Radiotherapy Plus Second-generation Antiandrogen for Oligometastatic Castration-resistant Prostate Cancer Patients.

Официальное название

Radioterapia estereotáctica Fraccionada más antiandrógeno de Segunda generación Para Pacientes oligometastásicos Con cáncer de próstata Resistente a la castración. Estudio español Fase II, Prospectivo, multicéntrico.

Обзор

The objectives of the study are to analyze the results obtained in survival, safety and quality of life after the combination of SBRT plus second-generation antiandrogen in patients diagnosed with metastatic castration-resistant prostate cancer in oligometastasis (≤5). Hence, the investigators evaluate the results of the combination of two widely used treatments in prostate cancer: SBRT plus the 'standard of care' for patients with mCRPC, second-generation antiandrogens (abiraterone and enzalutamide). Primary objective: Determine the PRFS measured from the time of initiation of second-generation antiandrogen to the time of radiological progression by choline PET/CT or 68Ga-PSMA PET/CT, in patients with mCRPC treated with the combination of second-generation antiandrogen plus SBRT. Secondary objectives: * Overall survival (time from initiation of second-generation antiandrogen to exitus) in patients with mCRPC treated with the combination of second-generation antiandrogen plus SBRT. * Quality of life of these patients using the European Organization for Research and Treatment of Cancer (EORTC) quality of life scale, EORTC QLQ-C30, validated for oncology patients. * Acute and chronic toxicity according to the "Common Terminology Criteria for Adverse Events" (CTCAEv5.0) scale. This is a phase II, multicenter, prospective, single group study in patients with castrate-resistant prostate cancer (CRPC). Patients will be recruited at the participant sites, after study approval and hospital authorization. 51 patients will be included in the study. Eligible patients will require: * Choline PET/CT or 68Ga-PSMA PET/CT, dated no more than 8 weeks prior to inclusion. * Clinical history, physical examination and functional evaluation scale (ECOG). * Geriatric assessment scale for patients \> 75 years (modified G8 scale) * Toxicity scale assessment (CTCAEv5.0) * Baseline quality of life questionnaire (EORTC QLQ-C30) (47) * Blood tests with complete blood count, coagulation, liver function, renal function, ions, alkaline phosphatase, PSA and total and free testosterone, dated no more than 4 weeks prior inclusion. * Inclusion/exclusion criteria assessment * Second generation antiandrogen prescription, chosen by the responsible physician according to clinical practice, in each case. Each patient will be included in the study once the second generation antiandrogen is initiated (which will be maintained until radiological progression, suspension due to poor tolerance and/or exitus). SBRT will be performed at least 2 weeks after initiating treatment with second generation antiandrogen, without exceeding 8 weeks from the start of treatment, and follow-up will continue up to a maximum of 36 months after completion of SBRT and/or exitus. Recruitment time is estimated at 36 months and a total follow-up time of 36 months. The total duration of the trial is therefore expected to be 6 years, to allow complete follow-up of the last patients included.

Вмешательства

• Препарат Xtandi
  Each patient will be included in the study once the second generation antiandrogen is initiated (which will be maintained until radiological progression, suspension due to poor tolerance and/or exitus)
• Препарат Zytiga® (Abiraterone Acetate)
  Each patient will be included in the study once the second generation antiandrogen is initiated (which will be maintained until radiological progression, suspension due to poor tolerance and/or exitus)
• Лучевая терапия SBRT
  SBRT will be performed at least 2 weeks after initiating treatment with second generation antiandrogen, without exceeding 8 weeks from the start of treatment, and follow-up will continue up to a maximum of 36 months after completion of SBRT and/or exitus

Первичные конечные точки

• Determine the PRFS [Срок оценки: From the start of the study (the day it begins) or up to 14 days before the start of the study (corresponding to the start of treatment with second-generation antiandrogens) until the time of radiological progression during follow-up, it can be up to 36.]

Вторичные конечные точки (3)

• Overall survival [Срок оценки: From the start of second-generation antiandrogen therapy (at baseline or up to 14 days prior) to the date of death from any cause, assessed up to 36 months.]
• Quality of life by EORTC scale [Срок оценки: from recruitment to the end of patient follow-up (up to 36 months)]
• Acute and chronic toxicity [Срок оценки: from recruitment to the end of patient follow-up (up to 36 months)]

Критерии участия

Критерии включения

• Patients with histologically prostate adenocarcinoma, confirmed with a biopsy.
• Testosterone in biochemical castration ranges (testosterone <50 ng/ml or 1.7 nmol/L) and documented progression: biochemical according to Phoenix criteria or distant by radiological confirmation (PSMA PET/CT or Choline PET/CT)
• Biochemistry progression confirmed according to Phoenix criteria, with testosterone in castration levels (testosterone <50 ng/ml or 1.7 nmol/L).
• Radiological confirmation (with choline-PET/CT or 68Ga-PSMA-PET/CT) of ≤5 node or bone metastasis, non-visceral, eligible to receive SBRT treatment (< 3 cm major diameter in bone metastases, < 5 cm in lymph node metastases). In the case of very close metastases, a limit of up to 5 treatment fields with SBRT is allowed, instead of 5 metastases.
• Patients candidate to receive treatment with abiraterone or enzalutamide as per clinical routine, and treatment selection and prescription assigned by responsible physician before the inclusion in the study. or or who has started treatment no more than 14 days prior to signing, as first-line treatment after a diagnosis of oligoresistance.
• Patients must provide written informed consent.
• Life expectancy > 3 months.

Критерии исключения

• Patients with prostate carcinoma with histology other than adenocarcinoma.
• No previous biopsy.
• > 5 metastasis, not approachables in 5 treatment fields
• Patients with visceral metastasis and or metastasis non elegible to receive SBRT.
• Patients with Testosterone above castration levels
• Patients with prior treatment with docetaxel as first-line CRPC treatment (previous docetaxel treatment is permitted when administered as hormone-sensitive metastatic prostate cancer treatment.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Испания · 15 центров

• Hospital Universitario Miguel Servet — Zaragoza
• Hospital Clinic de Barcelona — Barcelona
• Instituto Catalán de Oncología Hospitalet — L'Hospitalet de Llobregat
• Hospital Universitario Basurto — Bilbao
• Hospital Universitario De Salamanca — Salamanca
• Hospital Clínico Universitario De Valladolid — Valladolid
• Hospital De La Santa Creu I Sant Pau — Barcelona
• Consorci Sanitari De Terrassa — Terrassa
• … и ещё 7 центров

Публикации

• Shabason JE, Minn AJ. Radiation and Immune Checkpoint Blockade: From Bench to Clinic. Semin Radiat Oncol. 2017 Jul;27(3):289-298. doi: 10.1016/j.semradonc.2017.03.002. Epub 2017 Mar 16. PMID 28577836
• Uppal A, Ferguson MK, Posner MC, Hellman S, Khodarev NN, Weichselbaum RR. Towards a molecular basis of oligometastatic disease: potential role of micro-RNAs. Clin Exp Metastasis. 2014 Aug;31(6):735-48. doi: 10.1007/s10585-014-9664-3. Epub 2014 Jun 27. PMID 24968866
• Haffner MC, Mosbruger T, Esopi DM, Fedor H, Heaphy CM, Walker DA, Adejola N, Gurel M, Hicks J, Meeker AK, Halushka MK, Simons JW, Isaacs WB, De Marzo AM, Nelson WG, Yegnasubramanian S. Tracking the clonal origin of lethal prostate cancer. J Clin Invest. 2013 Nov;123(11):4918-22. doi: 10.1172/JCI70354. Epub 2013 Oct 25. PMID 24135135
• Reese AS, Feigenberg SJ, Husain A, Webb TJ, Hausner PF, Edelman MJ, Feliciano J, Tkaczuk KH, Sharma NK. Stereotactic Ablative Radiotherapy (SABR): Impact on the Immune System and Potential for Future Therapeutic Modulation. Mol Cell Pharmacol. 2013 Jan 1;5(1):19-25. PMID 25126157
• Lee Y, Auh SL, Wang Y, Burnette B, Wang Y, Meng Y, Beckett M, Sharma R, Chin R, Tu T, Weichselbaum RR, Fu YX. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood. 2009 Jul 16;114(3):589-95. doi: 10.1182/blood-2009-02-206870. Epub 2009 Apr 6. PMID 19349616
• Cox BW, Spratt DE, Lovelock M, Bilsky MH, Lis E, Ryu S, Sheehan J, Gerszten PC, Chang E, Gibbs I, Soltys S, Sahgal A, Deasy J, Flickinger J, Quader M, Mindea S, Yamada Y. International Spine Radiosurgery Consortium consensus guidelines for target volume definition in spinal stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2012 Aug 1;83(5):e597-605. doi: 10.1016/j.ijrobp.2012.03.009. Epub 2 PMID 22608954
• Conde-Moreno AJ, Lopez-Guerra JL, Macias VA, Vazquez de la Torre ML, Samper Ots P, San Jose-Maderuelo S, Pastor Peidro J, Lopez-Torrecilla J, Exposito-Hernandez J. Spanish Society of Radiation Oncology clinical guidelines for stereotactic body radiation therapy in lymph node oligometastases. Clin Transl Oncol. 2016 Apr;18(4):342-51. doi: 10.1007/s12094-015-1383-y. Epub 2015 Sep 2. PMID 26329294
• Lopez-Campos F, Cacicedo J, Counago F, Garcia R, Leaman-Alcibar O, Navarro-Martin A, Perez-Montero H, Conde-Moreno A. SEOR SBRT-SG stereotactic body radiation therapy consensus guidelines for non-spine bone metastasis. Clin Transl Oncol. 2022 Feb;24(2):215-226. doi: 10.1007/s12094-021-02695-6. Epub 2021 Oct 11. PMID 34633602

Идентификаторы

NCT: NCT07717268 · IRA-RAD-2022-001 · 2023-505024-62

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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